Valencia

Researchers are evaluating the combination of CGT9486 and sunitinib compared to sunitinib alone in patients with locally advanced, unresectable, or metastatic Gastrointestinal Stromal Tumors GIST. This Phase 3, open-label international trial involves multiple parts, including dose confirmation, drug interaction assessments, and efficacy comparisons. The study also includes substudies focusing on drug-drug interaction potential and first-line treatment in patients with specific genetic mutations KIT exon 9. Approximately 482 patients will participate across these parts.

Preterm birth, defined as birth before 37 weeks of gestation, occurs in about 8 percent of pregnancies in Canada and is linked to many health challenges, especially when it happens before 29 weeks. At this early stage, infants often face breathing difficulties and may require resuscitation. This trial compares resuscitation using either low 30% or high 60% oxygen levels to determine which approach results in better survival and neurodevelopmental outcomes at around 24 months of age. The study uses a cluster randomized crossover design where hospitals alternate between starting resuscitation with 30% or 60% oxygen for groups of 30 infants. Resuscitation includes standard care steps like lung expansion and ventilation support as needed. Oxygen is initially given at the assigned concentration for the first 5 minutes, then adjusted based on the infants oxygen saturation levels and heart rate over the next 5 minutes to maintain target saturation ranges. This approach aims to balance risks of too much or too little oxygen. Participants are infants born between 23 and 28 weeks gestation who receive full resuscitation at participating centers. During the study, infants have oxygen saturation monitored continuously, and adjustments to oxygen concentration are made carefully. Researchers will evaluate survival and major neurodevelopmental outcomes at 24 months corrected age, along with several safety and health measures during the neonatal intensive care stay. The trial is expected to provide important evidence to guide oxygen use during resuscitation of extremely preterm infants.

Chronic kidney disease CKD affects over 800 million people worldwide and leads to significant health challenges, including multiple secondary diseases, frequent hospital visits, and high costs. Recent advances have identified promising drugs like sodium-glucose co-transporter 2 inhibitors, finerenone, and semaglutide that may slow CKD progression. This study aims to evaluate whether a biomarker-guided treatment approach can better reduce kidney function decline compared to standard care in CKD patients with albuminuria. This prospective, randomized, open-label study plans to enroll 125 participants with CKD and albuminuria who will be randomly assigned to either a biomarker-targeted treatment group or a standard care group. In the treatment group, medications such as dapagliflozin, finerenone, and semaglutide will be added stepwise based on urinary biomarkers UACR and UEGF and individual response. After about four weeks on each drugs maximum tolerated dose, biomarker levels will be reassessed to decide whether to continue, switch, or add treatments. Participants will undergo regular evaluations of kidney function through estimated glomerular filtration rate eGFR and urinary biomarkers throughout the study, which lasts over two years. The main outcome measured is the change in eGFR slope from week 26 to week 104. Additional assessments include changes in eGFR and UACR from baseline to week 104 or 112. Safety and effectiveness of the biomarker-guided approach will be monitored carefully during the trial.

Researchers are evaluating new treatments for advanced renal cell carcinoma RCC, a type of kidney cancer. This study compares the effects of combining two targeted therapies, belzutifan and zanzalintinib, against belzutifan with a placebo. The goal is to see if the combination can help people live longer and prevent the cancer from getting worse after other treatments have failed. Participants will take 120 mg of belzutifan orally and either 60 mg of zanzalintinib or a matching placebo once daily for about 24 months. The study is randomized and double-blind, meaning neither participants nor researchers know who receives the active combination or placebo. Two groups are compared belzutifan plus zanzalintinib and belzutifan plus placebo. During the study, participants will be monitored for progression-free survival and overall survival, with assessments up to around 30 to 50 months. Researchers will also evaluate tumor response, duration of response, quality of life, and side effects. Safety and tolerability will be tracked throughout treatment and follow-up periods. The study is sponsored by Merck Sharp & Dohme LLC and aims to provide important information on treating advanced RCC.

Researchers are investigating new treatments for advanced renal cell carcinoma RCC that has returned after prior therapy. The study aims to find out if the combination of belzutifan and zanzalintinib can help people with recurrent advanced RCC live longer without their cancer worsening compared to the drug cabozantinib. This is a phase 3 randomized trial evaluating these treatments in participants who have experienced recurrence during or after prior anti-PD-1L1 therapy. Participants are randomly assigned to receive either belzutifan plus zanzalintinib taken orally once daily or cabozantinib taken orally once daily. They continue their assigned treatment until certain reasons require stopping the study intervention. The study compares the effects of these treatments on cancer progression and survival among people with advanced RCC who have had disease recurrence after adjuvant therapy. During the study, participants will be regularly monitored for progression-free survival and overall survival for up to about 73 months. Researchers will also assess tumor response, duration of response, adverse events, and quality of life using questionnaires over approximately 25 months. The study involves ongoing evaluations to understand how these treatments affect symptoms, functioning, and overall health during long-term follow-up.

Researchers are evaluating if combining the medicines calderasib and subcutaneous pembrolizumab can more effectively treat people with non-small cell lung cancer NSCLC that has a KRAS G12C mutation. The study aims to find out whether patients receiving calderasib with pembrolizumab live longer without their cancer growing or spreading compared to those receiving pembrolizumab with chemotherapy. This is a Phase 3 clinical trial focusing on first-line treatment for advanced or metastatic nonsquamous NSCLC. Participants are assigned to one of two groups. One group receives subcutaneous pembrolizumab plus berahyaluronidase alfa every 6 weeks for up to 18 cycles about 2 years along with oral calderasib until treatment discontinuation criteria are met. The other group receives the same pembrolizumab and berahyaluronidase alfa regimen plus chemotherapy with pemetrexed and either carboplatin or cisplatin infusions during the early cycles. Treatment continues based on individual response and tolerability. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess progression-free survival, overall survival, response rates, and quality of life using questionnaires and symptom scores over several years. Safety will be monitored through adverse event reporting. The trial lasts up to about 7 years with ongoing evaluation of health outcomes and side effects to understand the impact of these treatment combinations.

Researchers are studying treatments for locally advanced or metastatic colorectal cancer mCRC that cannot be removed by surgery and has a specific KRAS G12C gene mutation. This trial aims to evaluate if adding the targeted therapies calderasib and cetuximab to the standard chemotherapy regimen mFOLFOX6 can provide better outcomes compared to mFOLFOX6 with or without bevacizumab. The study focuses on the safety and tolerability of these combinations and whether they can help people live longer without their cancer growing or spreading. Participants will be assigned to one of two groups. One group will receive calderasib orally, cetuximab every two weeks, and mFOLFOX6 chemotherapy including oxaliplatin, leucovorin or levofolinate calcium, and 5-fluorouracil every two weeks. The other group will receive mFOLFOX6 chemotherapy with or without bevacizumab every two weeks, based on the investigators decision. Treatments will continue until certain stopping criteria are met. During the study, participants will be monitored for side effects and treatment tolerance, with regular assessments of cancer progression. Researchers will measure outcomes such as dose-limiting toxicities, adverse events, progression-free survival, and overall survival. Quality of life will also be evaluated through questionnaires. The study may last up to several years, with monitoring continuing for safety and effectiveness throughout the treatment period and follow-up.

Researchers are studying metastatic castration-resistant prostate cancer mCRPC to find new treatment options. This trial evaluates if the study medicine ifinatamab deruxtecan I-DXd or MK-2400 helps people live longer overall and experience slower cancer growth or spread compared to chemotherapy. The study is a Phase 3 trial comparing I-DXd with standard chemotherapy for mCRPC patients. Participants are randomly assigned to receive either I-DXd at 12 mgkg every 3 weeks through intravenous infusion or docetaxel chemotherapy at 75 mgm2 every 3 weeks combined with daily prednisone pills. Treatment continues until the disease progresses, unacceptable side effects occur, or treatment is stopped for other reasons. Premedication is given before each dose of I-DXd to help prevent nausea and vomiting. During the study, participants will have regular visits for treatment and monitoring. Researchers will assess overall survival and radiographic progression-free survival for up to about 36 months. Additional measures include response rates, time to pain progression, PSA progression, and adverse events. The study tracks safety, treatment effects, and quality of life over a long follow-up period to better understand the potential benefits and risks of I-DXd compared to chemotherapy.

Researchers are evaluating new treatment options for people living with HIV-1 Human Immunodeficiency Virus Type 1 who have not been treated before. The current standard treatment, antiretroviral therapy ART, involves taking multiple medicines daily and may cause other health problems. This study aims to compare a new study ART combining two medicines, islatravir and ulonivirine, taken once a week, against the standard daily ART to see if it works as well and is safe and tolerable. Participants will receive one of several treatments for 96 weeks the study ART with islatravir and ulonivirine taken once weekly, the standard ART with bictegraviremtricitabinetenofovir alafenamide BICFTCTAF taken once daily, or combinations involving placebos matching these treatments. The study includes two phases Phase 2 which is open-label, and Phase 3 which is double-blind and randomized. During the study, participants will have regular assessments including measuring the amount of HIV-1 RNA in their blood and monitoring for adverse events and medication tolerance. Researchers will evaluate how well the treatments control the virus and affect immune cells over 24, 48, and 96 weeks. Safety monitoring will continue for about 102 weeks. The total study duration for participants is up to 96 weeks of treatment plus follow-up.

Researchers are exploring new treatments for women with relapsed high-grade serous ovarian cancer, which is a fast-growing cancer starting in ovarian cells, the lining of the belly, or fallopian tubes. The study evaluates raludotatug deruxtecan R-DXd, a type of antibody drug conjugate, combined with other therapies, to understand safety, tolerability, and cancer response. This includes women with platinum-sensitive and platinum-resistant recurrent ovarian cancer who have had prior treatments. The study has two parts Part 1 involves gradually increasing doses of R-DXd combined with chemotherapy drugs like carboplatin, paclitaxel, bevacizumab, or pembrolizumab to find a recommended dose. Part 2 uses this recommended dose to further assess treatment effects. Participants receive intravenous infusions every three weeks, with chemotherapy cycles lasting up to about four months and pembrolizumab up to two years. The combinations vary depending on cancer sensitivity and treatment history. Participants undergo regular treatment visits where cancer response and side effects are monitored. Tumor tissue samples are collected before treatment. Researchers track adverse events, dose-limiting toxicities, and how long the cancer responds to treatment. The study lasts up to approximately three years, allowing for long-term safety and effectiveness assessments, with ongoing evaluation of participants health throughout the trial.